One of the most frequent complications of AIDS is Mycobacterial infections. The incidence of tuberculosis has dramatically increased in all countries as a result of the HIV epidemic. Lately, it has been found that the natural history of new Mycobacterium tuberculosis infection is accelerated by HIV disease. In a wide number of cases the emergence of Mycobacterium tuberculosis nosocomial outbreaks of drug-sensitive and drug-resistant strains has been reported in HIV infected patients. The inadequate efforts to provide complete therapy to this kind of patient has caused the emergence of multidrug-resistant tuberculosis, that is responsible for the increased mortality rate in AIDS patients. A renewed interest in mycobacterial infections has also been kindled by the occurrence of Mycobacterium avium infections in patients with acquired immunodeficiency syndrome. The role of Mycobacterium avium as a pathogen is actually confusing and controversial for clinicians who care for AIDS patients. Disseminated Mycobacterium avium infections occur in a high population of HIV infected patients with low CD4+ cell count. Recent studies reported that rifabutin significantly reduced the incidence of Mycobacterium avium bacteremia, although, new macrolides such as clarithromycin and azithromycin are also effective in the treatment of the infection. Therefore, because of the emergence of macrolides resistance, the use of combination therapy is highly recommended in the Mycobacterium avium infection management.